Chronic treatment of guinea pigs with 1-alpha-acetylmethadol (LAAM) increased a stereotyped behavior response to injected apomorphine and increased the amount of 3H-spiroperidol bound to membrane fragments isolated from the striata of the treated animals. LAAM and apomorphine failed to displace 3H-spiroperidol from these binding sites. These results suggest that the increased number of binding sites for 3H-spiroperidol as a result of chronic LAAM treatment is due to an action of LAAM remote from the sites labeled by 3H-spiroperidol. Experiments are in progress to test effect of LAAM on receptors selectively labeled by the dopamine agonist 3H-apomorphine. In the isolated guinea pig heart in vitro, LAAM depresses resting heart rate and force of contraction. In addition, LAAM inhibits release of norepinephrine in response to sympathetic nerve stimulation. Following chronic treatment the resting force of contraction is greater than in hearts isolated from control guinea pigs and greater amounts of norepinephrine are released by nerve stimulation. Experiments are in progress to test the role of calcium in these phenomena and to identify the receptors involved in the pharmacological effects of LAAM.